Mosquito-borne diseases kill millions of people each year. A team of scientists think genetic manipulation could wipe out the worst of them.

The nonprofit Target Malaria is trying to eliminate the worst of these illnesses, malaria, through genetic modification.

Target Malaria plans on testing its technology in Burkina Faso, Mali, and Uganda.

Some scientists have expressed concerns about gene drives, saying they could have devastating consequences on the environment.

Mosquitoes are the deadliest animals in the world, killing millions of people each year by infecting them with diseases like malaria, dengue fever, West Nile virus, and Zika.

Malaria, the deadliest of these diseases, leads to more than 430,000 deaths annually. It used to be even more common, but a combination of new drugs and insecticides led to a sharp drop in the early 2000s.

That drop has since stalled out, according to the World Health Organization. The global malaria rate has not changed much since 2013, in large part because affected areas are not receiving enough funding to fight the disease. Over time, mosquitoes also build up resistance to existing insecticides.

Many scientists agree that a new approach is needed to eliminate the disease, and researchers at the nonprofit Target Malaria think that genetic modification through “gene drives” is the way to do it. This process would reduce the number of female mosquitoes that transmit malaria.

Target Malaria is not the only organization experimenting with genetically modified mosquitoes, but its members believe they will release their technology first. The group has already selected three locations in Africa as testing sites.

Gene drives, which can change a gene to produce a specific trait that will show in a population for many generations, have sparked controversy in recent months. After much debate, a United Nations group ruled in November 2018 that gene drive research may proceed for now, though limitations have been put in place.

“We are on the cusp of a new bio-revolution,” one UN official, who requested anonymity, told The Guardian. “It is like we were using saws but now we are using scalpels. We can eradicate entire species and we can resurrect them like Jurassic Park. The change is mind-boggling. But it doesn’t always work 100%. There can still be unintended consequences.”

Delphine Thizy, the stakeholder engagement manager at Target Malaria, told Business Insider that the group won’t change its work in light of the UN resolution, as the language reinforces what her team is already doing.

“It’s a good text because it’s really balanced between these needs to continue the research and making sure we can answer the questions, the very valid questions on safety and efficacy, and at the same time provide some precaution about making sure the risk assessment is done,” Thizy said.

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People queue outside a health center as they wait to get treatment for malaria, in San Felix, Venezuela on November 10, 2017.

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William Urdaneta/Reuters

How gene drive technology works

There are thousands of mosquito species in the world, but very few pose a danger to humans.

Male mosquitoes don’t bite humans; only females infected with a virus or parasite can pass on that infection because they drink human blood to gather nutrients that help them produce eggs.

To reduce the number of female mosquitoes that infect people with malaria, Target Malaria scientists are focusing on a technology called CRISPR, which makes it possible to efficiently edit DNA.

Usually, only 50% of each generation’s offspring inherits DNA that is transmitted from one parent, which means that a trait’s frequency in a mosquito population stays the same from generation to generation. Gene drives, however, are inherited by a higher percentage of the offspring, making the modified trait more common as time goes on.

Target Malaria aims to bring the mosquito population down without killing off an entire species. The nonprofit is only going after Anopheles gambiae mosquitoes – which are responsible for the vast majority of malaria deaths in Africa – while leaving others alone.

“We are not trying to get them extinct, nor do we think it would be possible,” Thizy said.

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An Indian vegetable seller sells potatoes during smoke from fumigation being carried out to prevent the spread of mosquito-borne diseases in Allahabad, India, on November 1, 2018.

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Ritesh Shukla/NurPhoto via Getty Images

Target Malaria wants to test gene drives in three African countries

Thizy’s team is considering two main approaches: One would skew the sex ratio of mosquitoes to produce a population with at least 90% males. Another would target genes responsible for female reproduction to cause sterility.

These ideas are still being developed in labs. So far, the group has been successful in reducing the number of mosquitoes in a small cage, Thizy said.

Eventually, Target Malaria says it will apply a gene drive in three African countries – Mali, Burkina Faso, and Uganda.

In Uganda, the organization expects to soon open a lab building, Thizy said. The group is also studying wild-type mosquitoes to better understand how they behave.

Regulators in Mali are reviewing Target Malaria’s application for the use of sterile male mosquitoes in a lab. Thizy said these mosquitoes are not a tool for fighting malaria, but introducing them now can help scientists prepare for using gene drives later.

Target Malaria has also gotten permission to import sterile male mosquitoes to Burkina Faso. About 10,000 male mosquitoes are now waiting for release, and Thizy said she hopes they go out sometime this year. Regulators and local residents have signed off on the test, she said.

Thizy said Target Malaria will apply for permission to release the first gene drive in 2024 at the earliest, adding she doesn’t know how long it would take officials to approve the request.

“We are nowhere near making any release of gene drives in Africa or anywhere,” she said.

Other startups are also developing ways to wipe out mosquito-borne diseases

But other companies are also racing to control mosquito populations and eradicate diseases caused by the insect, including dengue fever and West Nile virus.

Verily, the life sciences unit of Google’s parent company, Alphabet, is targeting Aedes aegypti mosquitoes, which spread dengue fever and chikungunya in the tropics. Verily is infecting male mosquitoes with the bacterium Wolbachia, which prevents offspring from hatching.

Another Gates-backed company, Oxitec, is developing a male mosquito that can kill off future generations of malaria-transmitting females.

The UK-based company’s newest plan builds on its previous trials, which lowered the populations of mosquitoes that carry dengue, Zika, and other diseases. Oxitec’s mosquitoes have been dispatched in Brazil, Panama, and on the Cayman Islands, and have reduced wild populations of mosquitoes by around 90% in certain spots.

Still, these techniques aren’t perfect. In November 2018, the Cayman Islands suddenly called off future releases of genetically engineered mosquitoes in the area without providing a reason.

Some scientists say malaria can be eliminated without genetic modification

Ify Aniebo, a molecular geneticist who focuses on malaria drug resistance and has lived in Nigeria, wrote in Scientific American that Africans should have been consulted before the genetically modified mosquitoes were first developed, adding that scientists need to complete more studies on the safety and consequences of this technology.

It remains unclear if the introduction of these mosquitoes could cause new diseases to emerge. Aniebo said genetic modification is not necessary to eradicate malaria, pointing to Sri Lanka, which was declared malaria-free in 2016 without the use of such technology.

Thizy, though, said it is imperative to develop a new tool for malaria control because spending more money on insecticides and other existing methods isn’t going to work.

She said Target Malaria asks village residents for consent before conducting any tests. There is no evidence to suggest that any species relies on mosquitoes as a primary source of food, she added, though Target Malaria will independently work to confirm that.

“Should there be one, let’s imagine, the question to society and to regulators would be, is this species that might be affected important enough not to try a new tool for a disease that kills half a million people?” Thizy said. “And that is a societal decision.”